Excipient powders frequently exhibit poor flow and compaction behavior. Various techniques such as wet granulation, spray drying, mechanofusion, and grinding have been employed to improve the flow and compaction behavior.
U.S. Pat. No. 4,734,285 assigned to Dow Chemical Company discloses delayed release solid tablets of a therapeutically active composition and a process to prepare such a composition. Fine particles, which can pass through a 100 mesh screen (149 micrometer mesh size) and preferably 140 mesh screen (105 micrometer mesh size), of hydroxypropyl methylcellulose ether are present as an excipient in the tablet composition. These fine particles are very small in size and shows poor flow properties. Poor particle flow can lead to consolidation of the powder bed in processing equipment, such as storage bins and tablet press feed hoppers. Problems can include increased inconsistency in tablet weight or tablet crushing strength from tablet-to-tablet as well as inconsistency in the amount of active ingredient incorporated into each dosage form.
WO2004/022601 assigned to JRS Pharma LP and U.S. Pat. No. 5,585,115 assigned to Edward H. Mendell Co., Inc. disclose an agglomerated microcrystalline cellulose blend containing silicon dioxide, purported to have improved compressibility. The disclosure states that silicon dioxide is a critical component to improve compressibility. The two step process described includes spray granulation followed by wet granulation. The prepared granules in this process are further dried using heat, which is not advantageous. However, granulation is a time consuming and adds cost to the process, due to the time lost, additional labor, energy consumption and additional equipment required.
Several processes for drying-grinding moist cellulose derivatives are known in the art, such as described in the patent applications GB 2262527A; EP 0 824 107 A2; EP-B 0 370 447 (equivalent to U.S. Pat. No. 4,979,681); EP 1 127 895 A1 (equivalent to U.S. Pat. No. 6,509,461); EP 0 954 536 A1 (equivalent to U.S. Pat. No. 6,320,043); WO96/00748 A1; WO2011/046679 (equivalent to US 2012/187225) and WO2012/138532.
US2012/160944A1 assigned to ICEUTICA PTY LTD discloses a method to produce nano and micro-particle powders of a biologically active material which have improved powder handling properties using dry milling process.
WO2012/116402A1 assigned to University of Monash discloses binder powders for use in powder material processing and processes for their preparation by using techniques such as spray drying and mechanofusion. These processes lead to reduction in particle size of the polymer. Moreover, these processes are costly and time consuming
US2012/0178822A assigned to ISP INVESTMENTS INC discloses coprocessing of PVP and calcium silicate by using ball milling, spray drying or freeze drying.
The increase in flow of cellulose polymers by co-milling microcrystalline cellulose with nano-silica is described in J. Pharm. Sci. 2011 November; 100(11):4943-52, Chattoraj S, Shi L, Sun CC.
Moreover, spray drying, mechanofusion, magnetic assisted impaction, hybridizer, and grinding require specialized instruments that are commonly not available at manufacturing units.
Surprisingly, it has been found that bulk density and flowability of vinyl lactam derived polymers can be increased by a novel continuous process comprising coprocessing the polymer and a coprocessing agent using high shear.
Thus, the present invention relates to a coprocessed excipient composition comprising vinyl lactam derived polymer and a deagglomerated coprocessing agent. The coprocessed excipient is prepared in a continuous process and has excellent compactability and improved flow property as measured by Johanson flow rate number increase from 1.1 to 5.0 fold, is characterized by a Brookfield cohesion of less than 0.12 kPa and a bulk density of at least 0.249 g/ml. The coprocessing agent is fumed silica, colloidal silica, silicon dioxide, calcium silicate or a combination thereof.